Abstract
There have been a number of claims that high-dose administration of cocaine to rats leads to neurotoxic effects on dopamine neurons. In this study possible neurotoxic effects on monoamine neurons were examined by measuring the effects of cocaine (35 mg/kg daily for 10 days) on the binding of radioligands to uptake sites for dopamine, serotonin and norepinephrine using quatitative autoradiography. No effects of cocaine on any of the binding sites were observed and therefore, it is concluded that cocaine, unlike amphetamine derivatives which have similar pharmacologic properties, does not produce neurotoxic effects on monoamine neurons.
Similar content being viewed by others
References
Akimoto K, Hamamura T, Kazahaya Y, Akiyama K, Otsuki S (1990) Enhanced extracellular dopamine level may be the fundamental neuropharmacological basis of cross-behavioral sensitization between methamphetamine and cocaine — an in vivo dialysis study in freely moving rats. Brain Res 507:344–346
Appel NM, Mitchell WM, Contrera JF, De Souza EB (1990) Effects of high-dose fenfluramine treatment on monoamine uptake sites in rat brain: assessment using quantitative autoradiography. Synapse 6:33–44
Brunswick DJ, Tejani-Butt SM, Hauptmann M (1990) Effects of high-dose methamphetamine (MA) on norepinephrine (NE) and dopamine (DA) uptake sites in rat brain measured by quantitative autoradiography. Soc Neurosci Abstr 16:1111
De Souza EB, Battaglia G (1990) Effects of MDMA and MDA on brain serotonin neurons: evidence from neurochemical and autoradiographic studies. In: Asghar K, De Souza E (eds) Pharmacology and toxicology of amphetamine and related designer drugs. NIDA Research Monograph 94, pp 270–305
Feingold E, Seshadri SB, Tretiak O (1986) Hardware and software design considerations in engineering an image processing workstation: autoradiographic analysis with DUMAS and the BRAIN autoradiographic analysis software package. In: McEachron DL (ed) Experimental biology and medicine, vol 11. Functional mapping in biology and medicine. Karger, Basel, pp 175–203
Harvey JA, McMaster SE (1977) Fenfluramine: cumulative neurotoxicity after chronic treatment with low dosages in the rat. Commun Psychopharmacol 1:3–17
Harvey JA, McMaster SE, Yunger LM (1975) p-Chloroamphetamine: selective neurotoxic action in brain. Science 187:841–843
Hurd YL, Ungerstedt U (1989) Cocaine: an in vivo microdialysis evaluation of its acute action on dopamine transmission in rat striatum. Synapse 3:48–54
Izenwasser S, Cox BM (1990) Daily cocaine treatment produces a persistent reduction of [3H]dopamine uptake in vitro in rat nucleus accumbens but not in striatum. Brain Res 531:338–341
Javitch JA, Strittmatter SM, Snyder SH (1985) Differential visualization of dopamine and norepinephrine uptake sites in rat brain using [3H]mazindol autoradiography. J Neurosci 5:1513–1521
Karoum F, Suddath RL, Wyatt RJ (1990) Chronic cocaine and rat brain catecholamines: long-term reduction in hypothalamic and frontal cortex dopamine metabolism. Eur J Pharmacol 186:1–8
Kleven MS, Woolverton WL, Seiden LS (1988) Lack of long-term monoamine depletions following repeated or continuous exposure to cocaine. Brain Res Bull 21:233–237
Koe BK, Weissman A, Welch WM, Browne RG (1983) Sertraline, 1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4,-tetrahydro-1-naphthylamine, a new uptake inhibitor with selectivity for serotonin. J Pharmacol Exp Ther 226:686–700
Kovachich GB, Aronson CE, Brunswick DJ, Frazer A (1988) Quantitative autoradiography of serotonin uptake sites in rat brain using [3H]cyanoimipramine. Brain Res 454:78–88
Kovachich GB, Aronson CE, Brunswick DJ (1989) Effects of high-dose methamphetamine administration on serotonin uptake sites in rat brain measured using [3H]cyanoimipramine autoradiography. Brain Res 505:123–129
Mamounas LA, Molliver ME (1988) Evidence for dual serotonergic projections to neocortex: axons from the dorsal and median raphe nuclei are differentially vulnerable to the neurotoxin p-chloroamphetamine (PCA). Exp Neurol 102:23–36
Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, New York
Ritz MC, Lamb RJ, Goldberg SR, Kuhar MJ (1987) Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 237:1219–1223
Ryan LJ, Martone ME, Linder JC, Groves PM (1988) Cocaine, in contrast tod-amphetamine, does not cause axonal terminal degeneration in neostriatum and agranular frontal cortex of Long-Evans rats. Life Sci 43:1403–1409
Seiden LS, Ricaurte GA (1987) Neurotoxicity of methamphetamine and related drugs. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 359–366
Tejani-Butt SM, Bauer M, Brunswick DJ, Frazer A (1990a) Binding of [3H]-nisoxetine to rat brain: a new radioligand for norepinephrine uptake sites. Soc Neurosci Abstr 16:524
Tejani-Butt SM, Brunswick DJ, Frazer A (1990b) [3H]-Nisoxetine: a new radioligand for norepinephrine uptake sites in brain. Eur J Pharmacol 191:239–243
Trulson ME, Babb S, Joe JC, Raese JD (1986) Chronic cocaine administration depletes tyrosine hydroxylase immunoreactivity in the rat brain nigral striatal system: quantitative light microscopic studies. Exp Neurol 94:744–756
Trulson ME, Joe JC, Babb S, Raese JD (1987) Chronic cocaine administration depletes tyrosine hydroxylase immunoreactivity in the meso-limbic dopamine system in rat brain: quantitative light microscopic studies. Brain Res Bull 19:39–45
Trulson ME, Ulissey MJ (1987) Chronic cocaine administration decreases dopamine synthesis rate and increases [3H]spiroperidol binding in rat brain. Brain Res Bull 19:35–38
Yeh SY, DeSouza EB (1991) Lack of neurochemical evidence for neurotoxic effects of repeated cocaine administration in rats on monoamine neurons. Drug Alcohol Depend 27:51–61
Zetterstrom T, Sharp T, Marsden CA, Ungerstedt U (1983) In vivo measurement of dopamine and its metabolites by intracerebral dialysis: changes afterd-amphetamine. J Neurochem 41:1769–1773
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Benmansour, S., Tejani-Butt, S.M., Hauptmann, M. et al. Lack of effect of high-dose cocaine on monoamine uptake sites in rat brain measured by quantitative autoradiography. Psychopharmacology 106, 459–462 (1992). https://doi.org/10.1007/BF02244815
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244815